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Neurons 'lost to Alzheimer's' grown in lab

Research on Alzheimer’s disease is in the news today, with The Guardian reporting that “brain cells grown in the laboratory will help to identify new Alzheimer’s drugs”. The Mirror reports that Alzheimer’s patients could have their memory restored through transplants of the cells.

In this laboratory study, researchers managed to manipulate embryonic stem cells so that they developed into a type of nerve cell that is lost early on in Alzheimer’s disease, called basal forebrain cholinergic neurons (BFCNs).

Being able to grow these cells in the lab will make it easier for researchers to study them and understand their development. It should also assist in the study of what happens to these cells in Alzheimer’s disease, and help to identify drugs that could prevent the processes involved in the condition.

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However, much more research in animals is needed before transplants of these cells into humans could be considered. Researchers would need to be reasonably certain that the cells would be able to replace the lost cells in the correct area of the brain and work correctly, and that such a procedure was safe before any transplants were undertaken.

Where did the story come from?

The study was carried out by researchers from Northwestern University in Chicago. It was supported by grants from the National Institutes of Health and the Brinson Foundation. The study was published in the peer-reviewed journal Stem Cells.

The Guardian, Mirror and Daily Express reported this research. The Guardian focuses on how these cells could be used in the laboratory, and puts the findings into perspective by quoting one of the researchers as saying:

“I don’t want people to think that all of a sudden we have a treatment and a cure for Alzheimer’s disease, because we don’t. What we do have now is something that is going to be very helpful to get us there.”

The suggestions that “Alzheimer’s patients could soon have their memory restored with a transplant” in the Mirror and that an Alzheimer’s cure “is on the way” in the Express are premature.

What kind of research was this?

This laboratory study investigated whether researchers could manipulate stem cells to develop into a specific type of nerve cell that is lost early in the development of Alzheimer’s disease. These nerve cells are called basal forebrain cholinergic neurons (BFCNs). The loss of BFCNs is related to problems with spatial learning and memory. The researchers suggest that the ability to grow these brain cells in the laboratory could be a first step towards eventually using them to replace the lost cells in people with Alzheimer’s.

This type of research is important for developing techniques that may be useful in various ways. For example, cells generated in this way could be helpful in screening chemicals to identify those that might be helpful in preventing BFCN death in Alzheimer’s. Although, eventually, similar techniques might be used to generate cells for transplant into humans, much more research would be needed before this could be attempted.

What did the research involve?

The research was in human embryonic stem cells. The researchers tried two different techniques to try to get the stem cells to develop into BFCNs. First, they treated some of the cells with a sequence of chemicals known to promote the formation of nerve cells and to play a role in the developing forebrain. Second, they introduced DNA into other cells. This DNA carried instructions for making two proteins called Lhx8 and Gbx1, which control the development of BFCN cells. These proteins, called transcription factors, control the switching on of other genes.

The researchers then looked at whether cells treated in either way developed the characteristics of basal forebrain cholinergic neurons (BFCN), for example, whether the genes they had switched on were typical of BFCNs. They also looked at whether the cells could make connections with other nerve cells if they were grown with slices of mouse brain in the laboratory.

What were the basic results?

The researchers found that both methods produced cells with the characteristics of BFCN cells, although not all of the cells had these characteristics. The BFCN-like cells also produced acetylcholine, which is the chemical that BFCNs use for signalling to other nerve cells.

When these BFCN-like cells were purified and grown with slices of mouse brain in the laboratory, the BFCN-like cells migrated into the brain tissue, and grew the long projections called axons used by nerve cells to send signals to other nerve cells. For these axons to work properly they need to form a connection called a synapse with another cell. The researchers found that these axons did appear to form synapses with other nerve cells. Finally, they showed that the BFCN-like cells were sending electrical signals.

How did the researchers interpret the results?

The researchers concluded that they could selectively control the differentiation of human embryonic cells into basal forebrain cholinergic neurons (BFCNs). They say that this ability is a significant step towards understanding how these nerve cells develop. They say these cells may also aid in the rapid identification of experimental drugs that can help BFCN cells to survive, and therefore might have potential as treatments for Alzheimer’s disease.

Conclusion

This research has developed a new way of growing one type of nerve cell, which is important in Alzheimer’s, in the laboratory from stem cells. Being able to grow such cells in the laboratory should make it easier for researchers to study them and understand their development. It may also help uncover what happens to these cells in Alzheimer’s disease, and how this might be prevented or slowed.

The researchers suggest that these cells could eventually be used in transplants, but this prospect is likely to be a long way off. The brain is incredibly complex, and replacing its cells is likely to be a big challenge. Researchers would need to be reasonably certain that the cells would be able to replace the lost cells in the correct area of the brain, work correctly and have an impact on the brain’s function. They would also need to be sure that such a procedure was safe before any transplant could be attempted. A lot of research in animals is likely to be required before any such process could be tried in humans.

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